Adenylosuccinate synthase

In molecular biology, Adenylosuccinate synthase (or adenylosuccinate synthetase) (EC 6.3.4.4.) is an enzyme that plays an important role in purine biosynthesis, by catalysing the guanosine triphosphate (GTP)-dependent conversion of inosine monophosphate (IMP) and aspartic acid to guanosine diphosphate (GDP), phosphate and N(6)-(1,2-dicarboxyethyl)-AMP. Adenylosuccinate synthetase has been characterised from various sources ranging from Escherichia coli (gene purA) to vertebrate tissues. In vertebrates, two isozymes are present: one involved in purine biosynthesis and the other in the purine nucleotide cycle.

Structure

The crystal structure of adenylosuccinate synthetase from E. coli reveals that the dominant structural element of each monomer of the homodimer is a central beta-sheet of 10 strands. The first nine strands of the sheet are mutually parallel with right-handed crossover connections between the strands. The 10th strand is antiparallel with respect to the first nine strands. In addition, the enzyme has two antiparallel beta-sheets, composed of two strands and three strands each, 11 alpha-helices and two short 3/10-helices. Further, it has been suggested that the similarities in the GTP-binding domains of the synthetase and the p21ras protein are an example of convergent evolution of two distinct families of GTP-binding proteins.^[1] Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana when compared with the known structures from E. coli reveals that the overall fold is very similar to that of the E. coli protein.^[2]

Isozymes

Humans express two adenylosuccinate synthase isozymes:

adenylosuccinate synthase
Identifiers
Symbol	ADSS
Entrez	159
HUGO	292
OMIM	103060
RefSeq	NM_001126
UniProt	P30520
Other data
EC number	6.3.4.4
Locus	Chr. 1 q44

adenylosuccinate synthase like 1
Identifiers
Symbol	ADSSL1
Entrez	122622
HUGO	20093
OMIM	612498
RefSeq	NM_152328
UniProt	Q8N142
Other data
EC number	6.3.4.4
Locus	Chr. 14 q32.33

External links

Adenylosuccinate synthase at the US National Library of Medicine Medical Subject Headings (MeSH)

References

↑ Poland BW, Silva MM, Serra MA, Cho Y, Kim KH, Harris EM, Honzatko RB (December 1993). "Crystal structure of adenylosuccinate synthetase from Escherichia coli. Evidence for convergent evolution of GTP-binding domains". J. Biol. Chem. 268 (34): 25334–42. PMID 8244965.
↑ Prade L, Cowan-Jacob SW, Chemla P, Potter S, Ward E, Fonne-Pfister R (February 2000). "Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana". J. Mol. Biol. 296 (2): 569–77. doi:10.1006/jmbi.1999.3473. PMID 10669609.

This article incorporates text from the public domain Pfam and InterPro IPR001114

Purine metabolism

Anabolism

R5P→IMP:	Ribose-phosphate diphosphokinase Amidophosphoribosyltransferase Phosphoribosylglycinamide formyltransferase AIR synthetase (FGAM cyclase) Phosphoribosylaminoimidazole carboxylase Phosphoribosylaminoimidazolesuccinocarboxamide synthase IMP synthase

IMP→AMP:	Adenylosuccinate synthase Adenylosuccinate lyase reverse AMP deaminase

IMP→GMP:	IMP dehydrogenase GMP synthase reverse GMP reductase

Nucleotide salvage

Catabolism

Pyrimidine metabolism

Anabolism

CAD Carbamoyl phosphate synthase II Aspartate carbamoyltransferase Dihydroorotase

Dihydroorotate dehydrogenase Orotidine 5'-phosphate decarboxylase/Uridine monophosphate synthetase

CTP synthetase

Catabolism

Deoxyribonucleotides

Enzymes: CO CS and CN ligases (EC 6.1-6.3)

6.1: Carbon-Oxygen	Aminoacyl tRNA synthetase Alanine Arginine Asparagine Aspartate Cysteine D-alanine—poly(phosphoribitol) ligase Glutamate Glutamine Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine

6.2: Carbon-Sulfur	Succinyl coenzyme A synthetase Acetyl—CoA synthetase Long-chain-fatty-acid—CoA ligase

6.3: Carbon-Nitrogen	Glutamine synthetase Ubiquitin ligase Cullin Von Hippel–Lindau tumor suppressor UBE3A Mdm2 Anaphase-promoting complex UBR1 Glutathione synthetase CTP synthetase Adenylosuccinate synthase Argininosuccinate synthase Holocarboxylase synthetase GMP synthase Asparagine synthetase Carbamoyl phosphate synthetase I II Glutamate–cysteine ligase

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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